Diabetes is a serious, lifelong disease which can cause long-term complications that affect almost every part of the body. This disease often leads to blindness, heart and blood vessel disease, strokes, kidney failure, amputations, and nerve damage. Uncontrolled diabetes can complicate pregnancy, and birth defects are more common in babies born to women with diabetes. Diabetes is widely recognized as one of the leading causes of death and disability in the United States.
One important aspect in the treatment of diabetes is the tight control of blood glucose levels, which requires frequent monitoring of blood glucose levels of patients so as to manage food intake and the dosage and timing of insulin injection. Tests for determining serum glucose concentration typically require blood collection. Blood collection is an invasive technique requiring arterial or venous puncture. A patient has to endure discomfort associated with needles or other devices to obtain blood samples for testing. Currently, millions of diabetics are forced to draw blood daily to determine their blood sugar levels. In addition, blood collection sometimes can be associated with problems in various ethnic settings. To alleviate the constant discomfort and inconvenience for these individuals, substantial effort has been expanded in the search for a non-invasive or minimally invasive technology to accurately determine blood glucose levels, in particular for a non-invasive or minimally invasive to continuously or at least frequently monitor blood glucose levels.
In recent years, various non-invasive and minimally-invasive technologies have been proposed in the academic and patent literature to monitor blood glucose levels by determining glucose concentrations in an ocular fluid, such as tears, aqueous humor, or interstitial fluid. For example, PCT International Publication WO 01/13783, discloses that an ophthalmic lens comprising a chemical sensor can be used to determine the amount of an analyte (e.g., glucose) in an ocular fluid, which is accessible to light. Such chemical sensors comprise a receptor specific for an analyte of interest and a detectable label (e.g., a fluorescent label) which in combination with the receptor to provide a detectable optical signal (e.g., fluorescent signal). Fluorescent sensing system may provide a relatively high sensitivity for detecting a trace amount of an analyte of interest in a sample. However, there are some issues associated with fluorescent dyes. For instance, fluorescent dyes can be susceptible to photobleaching and therefore may not be photostable over a long period of time. Furthermore, a receptor needs to be labeled with a fluorescent label through a laborious and/or complicated process. Those issues may limit to some extend the practical application of the technologies described in WO 01/13783.
U.S. Pat. No. 6,120,460 to Abreu, in another example, suggests that a contact device containing miniaturized electrochemical sensor and placed on the front part of the eye can be used to measure glucose concentration in a tear fluid. The cost associated with miniaturization of electrochemical sensors may hinder the application of such technology.
An object of the invention is to provide an ophthalmic device, in particular, an implantable ophthalmic device, which contain a reflection hologram-based sensor for monitoring glucose levels in an ocular fluid. Such hologram-based sensor should be biocompatible and stable over a long period of time, especially when it is implanted in, on or about the eye or ocular vicinity.
Hologram-based sensors have been proposed in U.S. Pat. No. 5,989,923 and PCT International Publications WO 99/63408 and 01/50113. Those holographic chemical sensors proposed in the patent literature are largely based on a volume hologram, which is created in a silver halide-based recording material according to a process not suitable for mass, cost-effective production. Moreover, those holographic chemical sensors proposed in the patent literature may not be biocompatible so that they can not be implanted in, on or about the eye or ocular vicinity. In addition, a hologram recorded in a silver halide-based recording medium may not be stable over a long period of time, since silver halide may gradually leach out of an implantable ophthalmic device over time.
Another object of the invention is to provide a method for making a biocompatible holographic sensor. Such method can be used in large-scale, cost-effective production of biocompatible holographic sensors.